Monitoring mRNA vaccine antigen expression in vivo using PET/CT

被引：2

作者：

Blizard, Gabrielle S. ^{[1
,2
]}

Dwivedi, Garima ^{[3
,4
]}

Pan, Yi-Gen ^{[3
]}

Hou, Catherine ^{[1
]}

Etersque, Jean M. ^{[1
,2
]}

Said, Hooda ^{[5
]}

Chevrier, Anik ^{[6
]}

Lavertu, Marc ^{[6
]}

Ni, Houping ^{[3
,4
]}

Davis, Benjamin ^{[3
,4
]}

Tam, Ying ^{[7
]}

Cao, Quy ^{[8
]}

Mach, Robert H. ^{[1
]}

Weissman, Drew ^{[3
,4
]}

Alameh, Mohamad-Gabriel ^{[3
,4
,5
,9
]}

Sellmyer, Mark A. ^{[1
,2
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19014 USA

[3] Univ Penn, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19103 USA

[4] Univ Penn, Penn Inst RNA Innovat, Perelman Sch Med, Philadelphia, PA 19104 USA

[5] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA

[6] Polytech Montreal, Chem Engn Dept, Montreal, PQ, Canada

[7] Acuitas Therapeut, Vancouver, BC, Canada

[8] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA USA

[9] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

关键词：

LIPID NANOPARTICLES; OPTIMIZATION; DELIVERY; TAG;

D O I：

10.1038/s41467-025-57446-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Noninvasive visualization of the distribution and persistence of mRNA vaccine antigen expression in mammalian systems has implications for the development and evaluation of future mRNA vaccines. Here, we genetically fuse E. coli dihydrofolate reductase (eDHFR) to the delta furin diproline modified SARS-CoV-2 spike glycoprotein (S2P triangle f) mRNA vaccine and image its expression in female mice and male non-human primates using [18F]fluoropropyl-trimethoprim ([18F]FP-TMP). Whole body positron emission tomography (PET) imaging revealed transient expression of the vaccine antigen in the injection site and draining lymph nodes (dLNs). Fusion of eDHFR did not impact S2P immunogenicity and no humoral or cellular immune response was detected against eDHFR in either species. In this work, we show that eDHFR can be used as an mRNA-encoded PET reporter gene to monitor the spatiotemporal dynamics of mRNA vaccine antigen expression in vivo. This technique could be applied in clinical translation of future mRNA vaccines or therapeutics.

引用

页数：14

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